+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Investigating RNA expression profiles altered by nicotinamide mononucleotide therapy in a chronic model of alcoholic liver disease



Investigating RNA expression profiles altered by nicotinamide mononucleotide therapy in a chronic model of alcoholic liver disease



Human Genomics 13(1): 65



Chronic alcohol consumption is a significant cause of liver disease worldwide. Several biochemical mechanisms have been linked to the initiation and progression of alcoholic liver disease (ALD) such as oxidative stress, inflammation, and metabolic dysregulation, including the disruption of NAD+/NADH. Indeed, an ethanol-mediated reduction in hepatic NAD+ levels is thought to be one factor underlying ethanol-induced steatosis, oxidative stress, steatohepatitis, insulin resistance, and inhibition of gluconeogenesis. Therefore, we applied a NAD+ boosting supplement to investigate alterations in the pathogenesis of early-stage ALD. To examine the impact of NAD+ therapy on the early stages of ALD, we utilized nicotinamide mononucleotide (NMN) at 500 mg/kg intraperitoneal injection every other day, for the duration of a Lieber-DeCarli 6-week chronic ethanol model in mice. Numerous strategies were employed to characterize the effect of NMN therapy, including the integration of RNA-seq, immunoblotting, and metabolomics analysis. Our findings reveal that NMN therapy increased hepatic NAD+ levels, prevented an ethanol-induced increase in plasma ALT and AST, and changed the expression of 25% of the genes that were modulated by ethanol metabolism. These genes were associated with a number of pathways including the MAPK pathway. Interestingly, our analysis revealed that NMN treatment normalized Erk1/2 signaling and prevented an induction of Atf3 overexpression. These findings reveal previously unreported mechanisms by which NMN supplementation alters hepatic gene expression and protein pathways to impact ethanol hepatotoxicity in an early-stage murine model of ALD. Overall, our data suggest further research is needed to fully characterize treatment paradigms and biochemical implications of NAD+-based interventions.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 069602605

Download citation: RISBibTeXText

PMID: 31823815


Related references

Rat liver mitochondria can synthesize nicotinamide adenine dinucleotide from nicotinamide mononucleotide and ATP via a putative matrix nicotinamide mononucleotide adenylyltransferase. Biochemistry and Molecular Biology International 38(2): 297-306, 1996

Nicotinamide mononucleotide adenylyltransferase of pig-liver nuclei. The effects of nicotinamide mononucleotide concentration and pH on dinucleotide synthesis. Biochemical Journal 80: 318-323, 1961

Pyridine nucleotide cycle of Salmonella typhimurium: in vitro demonstration of nicotinamide mononucleotide deamidase and characterization of pnuA mutants defective in nicotinamide mononucleotide transport. Journal of Bacteriology 140(2): 607-611, 1979

The requirement for bivalent cations in formation of nicotinamide-adenine dinucleotide by nicotinamide mononucleotide adenylyltransferase of pig-liver nuclei. Biochemical Journal 101(1): 208-213, 1966

Hepatic protein Carbonylation profiles induced by lipid accumulation and oxidative stress for investigating cellular response to non-alcoholic fatty liver disease in vitro. Proteome Science 17: 1, 2019

Erythrocyte alterations as a model of free-radicals insult in patients with alcoholic and non alcoholic chronic liver disease. Hepatology 26(4 Part 2): 551A, 1997

Nicotinamide mononucleotide improves energy activity and survival rate in an in vitro model of Parkinson's disease. Experimental and Therapeutic Medicine 8(3): 943-950, 2014

Altered pharmacokinetics of rosiglitazone in a mouse model of non-alcoholic fatty liver disease. Drug Metabolism and Personalized Therapy 31(3): 165-171, 2016

Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer's disease-relevant murine model. Bmc Neurology 15: 19, 2015

Altered furosemide pharmacokinetics in chronic alcoholic liver disease with ascites contributes to diuretic resistance. Gastroenterology 92(2): 294-298, 1987

Altered hexokinase isoenzyme expression in alcoholic liver disease and primary biliary cirrhosis. Journal of Hepatology 23(Suppl. 1): 135, 1995

Clinicopathological characteristics and metabolic profiles of non-alcoholic fatty liver disease in Indian patients with normal body mass index: Do they differ from obese or overweight non-alcoholic fatty liver disease?. Indian Journal of Endocrinology and Metabolism 17(4): 665-671, 2013

Expression of genes for microRNA-processing enzymes is altered in advanced non-alcoholic fatty liver disease. Journal of Gastroenterology and Hepatology 28(8): 1410-1415, 2013

Altered fatty acid metabolism-related gene expression in liver from morbidly obese women with non-alcoholic fatty liver disease. International Journal of Molecular Sciences 15(12): 22173-22187, 2014

Profiles of antinuclear antibodies in chronic active hepatitis, primary biliary cirrhosis and alcoholic liver disease. Liver 4(2): 134-138, 1984